Compositionally different polymer-based sensor elements and methods for preparing same

ABSTRACT

The present invention provides a combinatorial approach for preparing arrays of chemically sensitive polymer-based sensors which are capable of detecting the presence of a chemical analyte in a fluid in contact therewith. The described methods and devices comprise combining varying ratios of at least first and second organic materials which, when combined, form a polymer or polymer blend that is capable of absorbing a chemical analyte, thereby providing a detectable response. The detectable response of the sensors prepared by this method is not linearly related to the mole fraction of at least one of the polymer-based components of the sensors, thereby making arrays of these sensors useful for a variety of sensing tasks.

This application is a continuation of U.S. patent application Ser. No.09/106,791, filed on Jun. 29, 1998 now U.S. Pat. No. 6,290,911, whichclaims benefit from the U.S. Provisional Application No. 60/051,203,filed on Jun. 30, 1997, the contents of which are expressly incorporatedherein by reference.

FIELD OF THE INVENTION

The present invention is directed to novel devices and methods forpreparing and using a plurality of compositionally different sensorsthat are capable of detecting the presence of a chemical analyte in afluid.

There is considerable interest in developing chemically sensitivesensors that are capable of detecting the presence of a particularchemical analyte in a fluid for the purpose of achieving a detectableresponse. Such sensors are often fabricated from a polymeric organicmaterial that is capable of absorbing a chemical analyte which comes incontact therewith, wherein absorbance of the analyte causes thepolymeric material to swell, thereby providing a response that iscapable of being detected. Variability in the ability to absorb ananalyte results in variability in the detectable signal produced. Suchorganic polymer-based sensors have found use in a variety of differentapplications and devices including, for example, devices that functionas analogs of the mammalian olfactory system (Lewis, U.S. Pat. No.5,571,401 (incorporated herein by reference), Lundström et al., Nature352:47–50 (1991) and Shurmer and Gardner, Sens. Actuators B 8:1–11(1992)), bulk conducting polymer films (Barker et al., Sens. Actuators B17:143 (1994) and Gardner et al., Sens. Actuators B 18:240 (1994)),surface acoustic wave devices (Grate et al., Anal. Chem. 67:2162 (1995),Grate et al., Anal. Chem. 65:A987 (1993) and Grate et al., Anal. Chem.65:A940 (1993)), fiber optic micromirrors (Hughes et al., J. Biochem.and Biotechnol. 41:77 (1993)), quartz crystal microbalances (Chang etal., Anal. Chim. Acta 249:323 (1991)) and dye impregnated polymericcoatings on optical fibers (White et al., Anal. Chem. 68:2191 (1996)).These and all other references cited herein are expressly incorporatedby reference as if set forth herein in their entirety. To date, however,many of the sensors employed in the above-described devices have beenfabricated from limited numbers of polymeric components and, therefore,are limited in the responses that they are capable of producing.

Further, today's technology lags far behind the ability of canines orhumans to detect or distinguish between chemical analytes. As aconsequence, certain work is limited by the suitability of animals orhumans to execute tasks. For example, quality control of food productscan require production line employees to smell each item. Unfortunately,the ability of individuals to adequately discriminate odors diminishesafter a short period of time, e.g., in about two hours. In addition,mammalian olfactory senses are limited in their ability to identifycertain vapors. For example, water vapor is not detectable by smell.Further, mammalian olfactory senses are limited to identifying gaseouscomponents, with no ability to identify or “smell” solutes in liquids.

There have been several attempts to construct sensors that can mimic orexceed the capability of olfactory organs. Such attempts have employed,for example, heated metal oxide thin film resistors, polymer sorptionlayers on the surfaces of acoustic wave resonators, fiber opticmicromirrors, arrays of electrochemical detectors, and conductivepolymers. Each of these techniques, however, has significant limitationsin reproducibility, the ability to discriminate between analytes, or thetime required for response. Further, these techniques are oftenprohibitively expensive or complicated.

Arrays of metal oxide thin film resistors, for example, are typicallybased on SnO2 films that have been coated with various catalysts.Furthermore, these arrays generally do not allow deliberate chemicalcontrol of the response of elements in the array and the reproducibilityof response from array to array is often poor. For example, the use ofsurface acoustic wave resonators, employs a signal transductionmechanism that involves complicated electronics and a frequencymeasurement to one Hz while sustaining a 200 MHz Rayleigh wave in thecrystal. Therefore, a need exists for devices and methods to identifyand measure analytes in fluids that overcome or minimize these problems.

Recent studies have shown that arrays of chemically sensitive sensors,formed from a library of swellable insulating organic polymerscontaining electrically conducting carbon black, are broadly responsiveto a variety of analytes, yet allow classification and identification oforganic vapors through application of pattern recognition methods.(Lonergan et al., Chem. Mater. 8:2298 (1996)). To date, these arrayelements have been fabricated from a relatively small number ofapproximately 10–20 organic polymers, with a single distinct polymerbackbone composition in each sensor element. Although a limited numberof polymeric sensor compositions might be chosen to perform optimallyfor specific applications, attempts to perform complex applications,such as to mimic the sense of olfaction, in which the sensing task istime dependent or is not defined in advance of the sensor arrayconstruction, will almost certainly require use of polymeric sensorlibraries that are far more extensive and compositionally diverse thanthose presently known. Thus, there is a need for novel methods forproducing large libraries of compositionally distinct chemicallysensitive sensors, each of which are capable of producing a detectableresponse in the presence of a chemical analyte of interest.

SUMMARY OF THE INVENTION

While methods for producing a plurality of compositionally distinctchemically sensitive sensors may prove to be very useful in a variety ofapplications, the utility of such methods is dependent upon whether theresponse produced by each of the compositionally distinct sensors is alinear function of the mole fraction of any particular component of thesensor. In other words, if the response provided by a sensor is a directlinear function of the mole fraction of a particular component of thesensor, then not much additional information will be obtained from theresponses of sensors that comprise a mixture of two different polymericmaterials over those sensors that are fabricated solely from one or theother polymeric material. Thus, nonlinearity in the response profile ascompared to the mole fraction of an organic material present in theplurality of the sensors is very important for increasing the power ofthese sensor arrays to resolve multitudes of analytes.

Therefore, it is an object of the present invention to provide acombinatorial approach to the construction of sensor arrays in whichblends of two or more organic materials are used as a feedstock tocreate compositionally varying chemically sensitive sensor films.

It is also an object of the present invention to provide (i) novelmethods for making and using a plurality of compositionally differentsensors, each of which comprise at least two different organic materialsand that are capable of detecting the presence of a chemical analyte ina fluid, and (ii) novel devices made by these methods.

It is another object of the present invention to provide (i) novelmethods for making and using a plurality of compositionally differentsensors, each of which provide a detectable signal in response to thepresence of a chemical analyte, and wherein the detectable signal is notlinearly related to the mole fraction of any organic material present inthe sensor; and (ii) novel devices made by these methods.

It is yet another object of the present invention to provide (i) novelmethods for making and using a plurality of chemically sensitive sensorsthat can be employed in any system that is dependent upon analyte uptaketo achieve a detectable response, and (ii) novel devices made by thesemethods. Such systems include, for example, analogs to the mammalianolfactory system, arrays of coated surface acoustic wave sensors, fiberoptic micromirrors, quartz crystal microbalance sensors, polymer-coatedfiber optic sensors, and the like.

It is another object of the present invention to provide (i) novelmethods for making a plurality of chemically sensitive sensors, whereinthose methods are quick, easy, inexpensive and are capable of providinglarge numbers of compositionally distinct sensors for use in vapordetection; and (ii) novel devices made by these methods.

These and further objects will be apparent to the ordinarily skilledartisan upon consideration of the specification as a whole.

In accordance with the present invention, novel methods are provided forpreparing a plurality of compositionally different sensors that arecapable of detecting the presence of a chemical analyte in a fluid, and,thereby, provide a detectable response. As used herein, the term “fluid”includes both gases and liquids. Specifically, an embodiment of thepresent invention is directed to methods for making a plurality ofcompositionally different sensors that are capable of detecting thepresence of an analyte in a fluid. The methods comprise combiningdifferent ratios of at least first and second organic materials. Thefirst and second organic materials will generally be different and forman organic polymer or polymer blend when combined, and the step ofcombining provides a plurality of compositionally different sensors thatcomprise a variable mixture of the first and second organic materials.Each of the sensors provides a detectable signal in response to thepresence of the chemical analyte, which signal is not linearly relatedto the mole fraction of at least one of the organic materials, and morepreferably both of the organic materials present in the sensors. Thedevices made by these methods are also disclosed.

In accordance with the present invention, the first and second organicmaterials may be combined simultaneously to produce the array ofsensors, or the organic components may be combined at different times toproduce the plurality of sensors, neither being critical to theinvention. In one embodiment, the first and second organic materials areeach organic polymers, thereby providing a plurality of sensors each ofwhich comprise an organic polymer blend. In another embodiment, thefirst and second organic materials may be organic monomer units which,when combined, polymerize, either with or without the presence of acatalyst, to form an organic polymer.

In still another embodiment, the first organic material is a homopolymeror copolymer, and the second organic material is a monomer which iscombined with the first material. When the monomer is polymerized in thepresence of the first, preformed polymer, the monomer polymerizes toproduce an interpenetrating network (IPN) of first and second organicmaterials. This technique is particularly suitable for achieving blendswhen dealing with polymers that are imicible in one another, and/orwhere the polymers are made from monomers that are volatile. Under theseconditions, the preformed polymer is used to dictate the properties(e.g., viscosity) of the polymer-monomer mixture. Thus, the polymerholds the monomer in solution. Examples of such systems are (1)preformed polyvinyl acetate with monomer methylmethacrylate to form anIPN of pVA and pMMA, (2) preformed pVA with monomer styrene to form anIPN of pVA and polystyrene, and (3) preformed pVA with acrylonitrile toform an IPN of pVA and polyacrylonitrile. More than one monomer may beused where it is desired to create an IPN having one or more copolymers.

In yet another embodiment of the present invention, an electricallyconductive material, which may be a single electrically conductivematerial or a mixture of two or more electrically conductive materials,is added to a polymer, polymer blend, or stabilized colloid. In apreferred embodiment of the present invention, the electricallyconductive material is a conductive polymer or carbon black. When anelectrically conductive material is added to the sensors, the sensorsprovide (i) an electrical path for an electrical current, (ii) a firstelectrical resistance in the electrical path in the absence of thechemical analyte and (iii) a second resistance in the electrical path inthe presence of the chemical analyte. The first and second electricalresistances may be either the same or different, depending upon theanalyte being analyzed and the ability of that sensor to sorb (eitherabsorb or adsorb) that analyte.

One embodiment is an electronic nose that mimics a mammalian olfactorysystem. This embodiment includes a substrate having a plurality ofsensors, where each sensor includes a chemically sensitive resistor thatincludes a combination of a first nonconductive organic material at aconcentration, a second nonconductive organic material at aconcentration and a conductive material. The first nonconductive organicmaterial is different from the second nonconductive organic material andthe number of array sensors is greater than the number of differentnonconductive organic materials which form the array sensors. Theelectronic nose also includes an electrical measuring apparatuselectrically connected to the array sensors.

Another embodiment of the electronic nose includes at least twochemically sensitive resistors and an electrical measuring apparatuselectrically connected to the resistors. Each chemically sensitiveresistor includes a combination of a first nonconductive organicmaterial at a concentration, a second nonconductive organic material ata concentration, and a conductive material, with the proviso that thefirst nonconductive organic material is different from the secondnonconductive organic material. In one embodiment, the concentration ofthe first nonconductive organic material of the first resistor isdifferent from the concentration of the first nonconductive organicmaterial of the second resistor. In another embodiment, the firstnonconductive organic material of the second resistor is the same as thefirst nonconductive organic material of the first resistor, and theconcentration of the first nonconductive organic material of the firstresistor is the same as the concentration of the first nonconductiveorganic material of the second resistor.

Methods of using the sensors are also provided. One embodiment is amethod for detecting the presence of an analyte in a fluid, whichincludes the step of providing a plurality of sensors that includes atleast two chemically sensitive resistors, each having a resistanceresponse to the presence of the fluid and a resistance response topresence of the analyte, and an electrical measuring apparatuselectrically connected to the resistors. Each chemically sensitiveresistor includes a combination of a first nonconductive organicmaterial at a concentration, a second nonconductive organic material,and a conductive material, with the proviso that the first nonconductiveorganic material in each resistor is different from the secondnonconductive organic material in each resistor and with a furtherproviso that the concentration of the first nonconductive organicmaterial in the first resistor is different from the concentration ofthe first nonconductive organic material in the second resistor. Theresistors are then exposed to the fluid, and resistance responses aremeasured. Then, the measured resistance response of the first resistoris compared to the first measured resistance response of the secondresistor to determine the presence of the analyte in the fluid.

In other embodiments, the sensors are combined with a wide variety ofsupporting technology to measure sensor response other than resistance.These embodiments include techniques that detect variations inelectromagnetic energy, optical properties, capacitance, inductance orimpedance and other physical, chemical and electrical properties thatmay vary in accordance with the response of the sensors. Thus, thenumber of applications sensing the presence of the analytes are verybroad and also, therefore, the applications to which the sensors may beput is very broad.

Methods of manufacturing are also provided. One embodiment is a methodof manufacturing an array of chemically sensitive sensors from a limitednumber of feedstock solutions of nonconductive organic materials inwhich the first step includes providing a first feedstock solution of afirst organic material at a concentration x in a first solvent, a secondfeedstock solution of a second organic material in a second solvent atthree different concentrations, y, y+b and y+c, and a substrate havingfirst, second and third preselected regions. Next, each of the first,second and third regions is contacted with the first feedstock solutionat concentration x. Then, the first region is contacted with the secondfeedstock solution at concentration y, the second region is contactedwith the second feedstock solution at said concentration y+b, and thethird region is contacted with the second feedstock solution at saidconcentration y+c. In this embodiment, the first organic material isdifferent from the second organic material and y, y+b and y+c are eachdifferent concentrations. The resulting sensor array has a total numberof sensors, one manufactured at each preselected region, that is greaterthan the number of feedstock solutions used to manufacture the sensors.

Other embodiments of the present invention are arrays of compositionallydifferent sensors and methods of producing them. In certain embodiments,these arrays of sensors may be incorporated into devices that arecapable of detecting the presence of an analyte in a fluid and/or may beplaced in communication with apparati that are capable of measuring thesignal produced by the array in response to the presence of a chemicalanalyte in a fluid. In some embodiments, the above-described pluralityof sensors is incorporated into a device designed to detect the presenceof an analyte in a fluid. Such devices include, for example, surfaceacoustic wave sensors, fiber optic micromirrors, quartz crystalmicrobalance sensors and polymer-coated fiber optic sensors.

Other embodiments of the present invention will become apparent to thoseof ordinary skill in the art upon a consideration of the specificationas a whole.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows the temporal response of a typical polymer compositechemiresistor sensor. This particular carbon black-containing compositesensor contained 55.1% poly(vinyl acetate) (PVA) and 44.9% poly(methylmethacrylate) (PMMA). The sensor was exposed to 13.9 parts per thousand(ppth) methanol in air for 540 seconds starting at the time pointdesignated 180 seconds in the graph.

FIG. 2 shows the maximum relative differential resistance response,ΔR_(max)/R, of a series of polymer blend carbon black-containingcomposite chemically sensitive resistors upon exposure to ethyl acetate.The plot depicts data obtained from 3 sensors of pure PMMA, 2 with 29.2%(by mole fraction) PVA, 2 with 55.1% PVA, 3 with 77.3% PVA and 2 of purePVA. The responses plotted for each sensor are the mean ΔR_(max)/Rvalues for 5 exposures to 2.9 ppth ethyl acetate in air. The error barsrepresent one standard deviation unit of the ΔR_(max)/R responsesaveraged over all of the sensors of a given composition. The dashed lineis a guide showing the deviation of the data points from linearity.

FIG. 3 shows a limited number (n) of polymer feedstock solutions at twodifferent concentrations that have been combined to produce a greaternumber of combinatorial sensors.

FIG. 4 shows the effect of increasing the variety polymer feedstocksolutions on the total number of sensors produced.

FIG. 5 depicts maximum relative differential resistance response,ΔR_(max)/R_(b), of a series of polymer blend-carbon black compositechemiresistors upon exposure to (a) 8.3 ppth of ethyl acetate. The plotof FIG. 5, as well as each of FIGS. 6–9, depict data obtained from 14detectors of pure PMMA, 10 with 11% (by monomer mole fraction) PVA, 10with 28% PVA, 15 with 44% PVA, 10 with 64% PVA, 15 with 78% PVA, 10 with91% PVA, and 15 of pure PVA. The responses plotted for each molefraction are the mean ΔR_(max)/R_(b) values for 10 exposures to each setof detectors containing the specified mole fraction of PVA, while theerror bars represent one standard deviation unit. Dashed lines weredrawn, joining the end points, as a guide to the eye indicating a linearresponse relationship.

FIG. 6 depicts maximum relative differential resistance response of aseries of polymer blend-carbon black composite chemiresistors uponexposure to 5.2 ppth of ethanol.

FIG. 7 depicts maximum relative differential resistance response of aseries of polymer blend-carbon black composite chemiresistors uponexposure to 8.2 ppth of acetonitrile.

FIG. 8 depicts maximum relative differential resistance response of aseries of polymer blend-carbon black composite chemiresistors uponexposure to 20.7 ppth of acetone.

FIG. 9 depicts maximum relative differential resistance response of aseries of polymer blend-carbon black composite chemiresistors uponexposure to 11.3 ppth of methanol in air.

FIG. 10 depicts temporal resistance response of a typical polymercomposite chemiresistor detector. This particular carbon black compositedetector contained 64% PVA and 36% PMMA by monomer mole fraction. Thedetector was exposed to 11.3 ppth of methanol in air for 600 s startingat t=120 s. The baseline resistance before the exposure R_(b), and themaximum resistance change during the exposure, ΔR_(max), were 4858 and50 Ω, respectively.

DETAILED DESCRIPTION OF THE INVENTION

Novel methods are provided for manufacturing large numbers of chemicallysensitive sensors starting from only a few base components. Specificembodiments are directed to methods of making and using a plurality ofcompositionally different polymer-based sensors that are capable ofdetecting the presence of an analyte in a fluid. Other embodiments aredirected to the devices made by these methods. In one embodiment, thesensors prepared using the presently described method comprise a polymeror polymer blend material that is capable of sorbing a chemical analytewhen, brought in contact therewith. In certain embodiments, the act ofsorbing the chemical analyte causes the polymer or polymer blend toswell, thereby providing a response that is capable of being detected.Such swelling causes a volumetric change in the sensor. In embodimentswhere the sensor is a chemically sensitive resistor, such swellingcauses a resistance response to permeation by the analyte. In certainembodiments, the resistance response is inversely proportional to thevolumetric change. Because different polymers and polymer blends exhibitvarying abilities to absorb different chemical analytes, arrays ofcompositionally distinct sensors will provide different responses todifferent analytes, those responses being capable of being detected andmeasured with an appropriate detection apparatus.

In order to prepare a plurality of compositionally different sensors asdescribed herein, different ratios of at least first and second organicmaterials must be combined to form an organic polymer or an organicpolymer blend. Organic materials that find use herein include organicpolymers, and particularly nonconductive organic polymers, which arecapable of absorbing a chemical analyte when brought into contacttherewith as well as organic monomeric units which, when combined,polymerize to form an organic polymer. In the case where two or moreorganic polymers are combined to form a plurality of sensors, eachsensor in the plurality will comprise a polymer blend (i.e., a blend oftwo or more different organic polymers). The two or more polymers addedto form the polymer blend may be combined either simultaneously or oneor more of the components may be added to the blend at different times.Preferably, only two different organic polymers are combined in varyingratios to form the plurality of sensors; however, three or moredifferent polymers may also be employed.

In certain embodiments where the organic materials combined to form thesensors are monomers, those monomers, when combined or whensignificantly heated, exposed to light, etc., polymerize to form asingle organic polymer. Again, as with the organic polymers discussedabove, the monomer units may be added to create the sensorssimultaneously or at different times. In other embodiments, the organicmaterials can be components of the same copolymer (a polymer made fromtwo or more different monomers). In certain embodiments, the organicmaterial can be oligomers. Certain embodiments of oligomers can havemolecular weights between 400 and about 2,000. In still otherembodiments, the organic material is a homopolymer (a polymer made fromone monomer).

In still another embodiment, the first organic material is a homopolymeror copolymer, and the second organic material is a monomer which iscombined with the first material. When the monomer is polymerized in thepresence of the first, preformed polymer, the monomer polymerizes toproduce an interpenetrating network (IPN) of first and second organicmaterials. This technique is particularly suitable for achieving blendswhen dealing with polymers that are imicible in one another, and/orwhere the polymers are made from monomers that are volatile. Under theseconditions, the preformed polymer is used to dictate the properties(e.g., viscosity) of the polymer-monomer mixture. Thus, the polymerholds the monomer in solution. Examples of such systems are (1)preformed polyvinyl acetate with monomer methylmethacrylate to form anIPN of pVA and PMMA, (2) preformed pVA with monomer styrene to form anIPN of pVA and polystyrene, and (3) preformed pVA with acrylonitrile toform an IPN of pVA and polyacrylonitrile. More than one monomer may beused where it is desired to create an IPN having one or more copolymers.

Thus, the term “organic materials” is intended to encompass both organicpolymers, and particularly nonconductive organic polymers, and monomers,which are capable of polymerizing to form an organic polymer.

A variety of different organic polymers may be employed as organicmaterials in the chemically sensitive sensors described herein. Certainof these polymers are discussed in Lewis et al., U.S. Pat. No.5,571,401, incorporated herein by reference in it entirety for allpurposes. In certain embodiments, the organic materials includemain-chain carbon polymers such as poly(dienes), poly(alkenes),poly(acrylics), poly(methacrylics), poly(vinyl ethers), poly(vinylthioethers), poly(vinyl alcohols), poly(vinyl ketones), poly(vinylhalides), poly(vinyl nitriles), poly(vinyl esters), poly(styrenes),poly(arylenes), and the like, main-chain acrylic heteroatom organicpolymers such as poly(oxides), poly(carbonates), poly(esters),poly(anhydrides), poly(urethanes), poly(sulfonates), poly(siloxanes),poly(sulfides), poly(thioesters), poly(sulfones), poly(sulfonamides),poly(amides), poly(ureas), poly(phosphazenes), poly(silanes),poly(silazanes), and the like, and main-chain heterocyclic polymers suchas poly(furan tetracarboxylic acid diimides), poly(benzoxazoles),poly(oxadiazoles), poly(benzothiazinophenothiazines),poly(benzothiazoles), poly(pyrazinoquinoxalines),poly(pyromellitimides), poly(quinoxalines), poly(benzimidazoles),poly(oxindoles), poly(oxoisoindolines), poly(dioxoisoindolines),poly(triazines), poly(pyridazines), poly(piperazines), poly(pyridines),poly(piperidines), poly(triazoles), poly(pyrazoles), poly(pyrrolidines),poly(carboranes), poly(oxabicyclononanes), poly(dibenzofurans),poly(phthalides), poly(acetals), poly(anhydrides), carbohydrates, andthe like. In a preferred embodiment, the polymers employed arepoly(vinyl acetate) (PVA) and poly(methacrylate) (PMMA). Each of theabove organic polymers, and the monomer units that polymerize to formthese polymers, are well known in the art and may be employed.

The organic materials employed are combined in different ratios so as toprovide a plurality of sensors, each of which contains a different molefraction of at least one of the organic materials employed in thefabrication. For example, a plurality of different sensors may beprepared by adding one part of a first polymer to 99 parts of a secondpolymer to provide the first sensor, adding two parts of a first polymerto 98 parts of a second polymer to provide the second sensor, etc.Therefore, each sensor in the plurality of sensors may becompositionally different.

The sensors are capable of providing a detectable signal in the presenceof a chemical analyte of interest. It is a preferred characteristic ofthe sensors that the detectable signal, or response, is not linearlyrelated to the mole fraction of at least one of the organic materialspresent in the sensor elements. Further, the response is not a sum oraverage of the individual responses of each of the components of thesensor. Such non-linearity in response is preferable because arrays ofcompositionally different sensor elements will optimally provideadditional information and resolution of detection if non-linearity ofresponse exists. In other words, if the magnitude of the detectablesignal is linearly related to the mole fraction of the componentspresent in the sensor elements, not much additional information can beobtained from sensors comprising a mixture of two different componentsas compared to that which can be obtained by using only two sensors,each of which being fabricated from only a single polymer component.Thus, the detectable signal produced by the sensor is not linearlyrelated to the mole fraction of at least one of the organic materialsused during sensor fabrication.

The step of combining the polymers or monomer units can be performed bya variety of different techniques such as, but not limited to, solutioncasting, suspension casting, and mechanical mixing. In general, solutioncast routes are advantageous because they provide homogeneous structuresand ease of processing. With solution cast routes, sensors may be easilyfabricated by spin, spray or dip coating. Suspension casting stillprovides the possibility of spin, spray or dip coating but moreheterogeneous structures than with solution casting are expected. Withmechanical mixing, there are no solubility restrictions since itinvolves only the physical mixing of the sensor element components, butdevice fabrication is more difficult since spin, spray and dip coatingare no longer possible. A more detailed discussion of each of thesefollows.

For systems where the components of the sensors are soluble in a commonsolvent, the sensors can be fabricated by solution casting. Inembodiments where sensors, for example, polymers, are soluble in acommon solvent, the use of such miscible solutions has an addedadvantage. In a series of test tasks, the resolving power of a sensorarray containing miscible blends was shown to be superior to that ofarrays containing an identical number of sensors that are comprised ofonly the two base polymeric materials.

In suspension casting, one or more of the components of the sensor issuspended and the others dissolved in a common solvent. Suspensioncasting is a rather general technique applicable to a wide range ofspecies, which can be suspended in solvents by vigorous mixing orsonication. Mechanical mixing is suitable for all of the possiblecomponent permutations. In this technique, the components are physicallymixed in a ball-mill or other mixing device.

In one embodiment, the combining step is performed by spraying a firstpolymer or monomer in a left to right direction across a grid whichcomprises multiple wells, wherein the concentration of the first polymeror monomer is smoothly varied as the spray travels across the grid. Oncethe first polymer or monomer is applied to the surface of the grid, asecond polymer or monomer is sprayed from a top to bottom directionacross the surface of the grid, wherein the concentration of the secondpolymer or monomer is smoothly varied as the spray travels across thesurface of the grid. This process provides a plurality of polymer- orpolymer blend-based sensor elements, each of which comprises a differentmole fraction of the first and/or second polymer or monomer employed inthe fabrication.

An embodiment of a method for manufacturing an array of chemicallysensitive sensors from a limited number of feedstock solutions ofnonconductive organic materials can be carried out by the followingmethod. First, the following are provided: a first feedstock solution ofa first organic material at a concentration x in a first solvent, asecond feedstock solution of a second organic material in a secondsolvent at three different concentrations, y, y+b and y+c, and asubstrate having first, second and third preselected regions. In someembodiments, these preselected regions are physically separated on thesubstrate. In certain embodiments, the regions are recessed below thesurface of the substrate forming wells. In other embodiments, ridgessurround the regions on the surface of the substrate. In some of theseembodiments, the ridges are formed from photodefinable material. Inother embodiments, the ridges are formed from sputtered material.

Next, each of the first, second and third regions is contacted with thefirst feedstock solution at concentration x. Then, the first region iscontacted with the second feedstock solution at concentration y, thesecond region is contacted with the second feedstock solution at saidconcentration y+b, and the third region is contacted with the secondfeedstock solution at said concentration y+c. In this embodiment, thefirst organic material is different from the second organic material andy, y+b and y+c are each different concentrations. The resulting sensorarray has a total number of sensors, one manufactured at eachpreselected region, that is greater than the number of feedstocksolutions used to manufacture the sensors.

In a preferred embodiment, the method of contacting is spraying. Inother embodiments, the method of contacting includes pipetting,micropipetting, depositing, spinning, evaporating, dipping, flowing andthe like. In some embodiments, the method further includes the step ofvarying the concentration of the second organic material in the secondsolution from y to y+b or from y+b to y+c. In certain of theseembodiments, the concentration is smoothly varied. In yet otherembodiments, after the step of varying the concentration, the methodfurther includes the step of moving the solution from the first regionto the second region. For instance, in certain embodiments usingspraying as the contacting method, a spraying unit contacts the first,second and third regions and delivers the first solution atconcentration x. Then a spraying unit contacts the first region anddelivers the second solution at concentration y. Then the concentrationis smoothly varied to concentration y+b as the second solution is movedto the second region and contacts the second region delivering thesolution at concentration y+b. Finally, the concentration is smoothlyvaried to concentration y+c as the second solution is moved to the thirdregion and contacts the third region delivering the solution at y+c. Incertain embodiments where the sensors to be produced are chemicallysensitive resistors, the first feedstock solution further comprises aconductive material, or a third feedstock contains said conductivematerial, which can also be varied in concentration.

In certain embodiments, these preselected regions are arranged in anarray or grid. In some embodiments, the concentrations of bothnonconductive organic materials are varied. As a simple example, anembodiment is formed where 4 sensors are arranged in a square grid withthe first sensor in the upper left corner, the second sensor in theupper right corner, the third sensor in the bottom left corner and thefourth sensor in the bottom right corner. The previously describedspraying unit or units can be used as described above to form thesensors. The first solution is sprayed from top to bottom with theconcentration smoothly varied from x to x+a. Then the second solution issprayed from left to right with the concentration smoothly varied from yto y+b. The resulting combinatorial sensor array contains four sensors,each with a different mole fraction of first and second organicmaterials. In some embodiments, the direction of spraying is altered. Inother embodiments, sensor arrays contain more than 4 sensors. Someembodiments can contain 10⁶ sensors. In certain embodiments, sensorarrays are arranged in shapes other than squares. For instance, arraysmay be arranged in shapes such as rectangles, circles, ovals, triangles,rhomboids, diamonds and the like. In some embodiments, arrays arearranged in shapes that produce the most sensors when the array isfabricated on a silicon wafer.

In certain embodiments, the organic materials can be polymers. Where theorganic materials are polymers, in certain embodiments, the firstpolymer is different from the second polymer. In other embodiments, theorganic materials are monomers, and the method further includes the stepof polymerizing the monomers by applying an activating agent. Theseactivating agents include light, heat and chemicals. In someembodiments, the first solution is miscible in the second solution. Incertain of these embodiments, the first solvent is the same as thesecond solvent.

The sensors that are prepared by these methods are capable of providinga detectable signal in response to contact with a chemical analyte.Specifically, the polymer-based sensors are capable of absorbing achemical analyte which, in some embodiments, causes the polymer toswell, thereby providing a signal which is capable of detection.Numerous apparati are known in the art and/or may be configured todetect the swelling of the sensor.

In a preferred embodiment, an electrically conductive material is addedto the polymer or polymer blend used to fabricate the sensors. In otherembodiments, two or more electrically conductive materials are added tothe organic material. In these cases, the sensors formed are chemicallysensitive resistors.

FIGS. 3 and 4 demonstrate the important concept of using a limitednumber of feedstock solutions to create a greater number of arraysensors. Referring now to FIG. 3, this shows a limited number (n) ofpolymer feedstock solutions that have been combined to produce a greaternumber of combinatorial sensors. The feedstock solutions along the topof the matrix (P₁ . . . P_(n)) are at concentration [x]. The samefeedstock polymers are shown along the left side of the matrix (P₁ . . .P_(n)) at concentration [y]. Individual cells in the matrix show theeffect of combining the feedstock solutions to produce a sensor. Forinstance, the cell at column 2, row 1 contains sensor P_(2[x])P_(1[y]),indicates that this sensor is formed from polymer feedstock P₂ atconcentration [x ]and polymer feedstock P₁ at concentration [y]. Ofcourse, the cells along the diagonal contain only one polymer type and,accordingly, are not combinatorial sensors. Thus, it can be seen that alimited number of polymer feedstock solutions can be combinatoriallycombined to produce a greater number of sensors. For instance, if thematrix is limited to a 4×4 array of feedstock solutions P₁ through P₄,such an array of 4 polymer feedstocks would produce 12 combinatorialsensors, assuming that x and y are different concentrations. Further, ifthe array is confined to those sensors in the cells above the diagonalin the 4×4 array, it can be seen that the four feedstocks still producea greater number of sensors, namely 6. Thus, even if we eliminatesensors that differ from another sensor only in the concentration of thefeedstock polymers used, the resulting number of sensors is stillgreater than the number of feedstock solutions.

Referring now to FIG. 4, the effect of increasing the variety polymerfeedstock solutions is shown. The feedstock solutions along the top ofthe matrix, P₁ . . . P_(n) at concentration [x], are the same as in FIG.3 above. However, here in FIG. 4, the feedstock polymers shown along theleft side of the matrix, P_(n+1), . . . P_(n+m) at concentration [y],are different from the feedstock polymers shown along the top of thematrix. As a result, the sensors in the cells along the diagonal nowcontain combinatorial sensors, in contrast to the diagonal cells of FIG.3. For instance, the cell at column 2, row 2 contains sensorP_(2[x])P_(n+2[y]), indicating that this sensor is formed from polymerfeedstock P₂ at concentration [x ]and polymer feedstock P_(n+2), whichis different from P₂, at concentration [y]. Thus, if this matrix islimited to a 4×4 array of feedstock solutions P₁ through P₄, along thetop, and P_(n+1) . . . P_(n+4) along the left, such an array of 8polymer feedstocks would produce 16 combinatorial sensors, regardless ofwhether x and y are different or the same concentrations.

The limited feedstock concept is demonstrated in an embodiment of anelectronic nose that mimics a mammalian olfactory system, that includesa substrate having a plurality of array sensors, where each array sensorincludes a chemically sensitive resistor that includes a combination ofa first nonconductive organic material at a concentration, a secondnonconductive organic material at a concentration, and a conductivematerial. The first nonconductive organic material is different from thesecond nonconductive organic material and the number of array sensors isgreater than the number of different nonconductive organic materialsthat form the array sensors. The electronic nose also includes anelectrical measuring apparatus electrically connected to the arraysensors. In certain embodiments, the first array sensor differs from thesecond array sensor in the concentration of the first nonconductiveorganic material.

Another embodiment includes two chemically sensitive resistors and anelectrical measuring apparatus electrically connected to the resistors.Each chemically sensitive resistor includes a combination of a firstnonconductive organic material at a concentration, a secondnonconductive organic material at a concentration, and a conductivematerial, with the proviso that the first nonconductive organic materialis different from the second nonconductive organic material and that theconcentration of the first nonconductive organic material of the firstresistor is different from the concentration of the first nonconductiveorganic material of the second resistor. In certain of theseembodiments, the first nonconductive organic material of the firstresistor is different from the first nonconductive organic material ofthe second resistor. In other embodiments, the second nonconductiveorganic material of the first resistor is different from the secondnonconductive organic material of the second resistor.

Yet another embodiment includes two chemically sensitive resistors andan electrical measuring apparatus electrically connected to theresistors. As described previously, each chemically sensitive resistorincludes a combination of a first nonconductive organic material at aconcentration, a second nonconductive organic material at aconcentration, and a conductive material, with the proviso that thefirst nonconductive organic material is different from the secondnonconductive organic material. However, in this embodiment, the firstnonconductive organic material of the first resistor is the same as thefirst nonconductive organic material of the second resistor, and theconcentration of the first nonconductive organic material of the firstresistor is the same as the concentration of the first nonconductiveorganic material of the second resistor. In certain embodiments, theconcentration of the second nonconductive organic material of the firstresistor is different from the concentration of the second nonconductiveorganic material of the second resistor. In other embodiments, thesecond nonconductive organic material of the first resistor is differentfrom the second nonconductive organic material of the second resistor.

Yet another embodiment is a single sensor for detecting an analyte in afluid, which includes a chemically sensitive resistor having aresistance, where the resistor includes a combination of a firstnonconductive organic material having a resistance, a secondnonconductive organic material having a resistance, and a conductivematerial. The resistance is initially a baseline resistance, when thesensor is free of the analyte. When the sensor is exposed to theanalyte, the resistance is a resistance response. An electricalmeasuring apparatus is electrically connected to the resistor. Theresistance of this resistor is nonlinear. In other words, the resistanceis different from a sum of the resistance of the first nonconductiveorganic material and the resistance of the second nonconductive organicmaterial, and further is different from an average of the resistance ofthe first nonconductive organic material and the resistance of thesecond nonconductive organic material.

In certain embodiments, the first and second nonconductive organicmaterials are nonconductive organic polymers and the combination is anorganic nonconductive polymer blend. Lists of these organic polymershave previously been cited herein. In one embodiment, the firstnonconductive polymer is polyvinyl acetate and the second nonconductivepolymer is polymethyl methacrylate. In other embodiments, thenonconductive organic materials are each nonconductive organic monomers,and the combination polymerizes the monomers into an organic polymer. Incertain embodiments, the first nonconductive organic monomer isdifferent from the second nonconductive organic monomer. In otherembodiments, they are the same.

One or more of a variety of electrically conductive materials may beemployed. In some embodiments, the conductive material is an organicconducting polymer. Examples of such organic conducting polymers includepoly(anilines), poly(thiophenes), poly(pyrroles), poly(acetylenes), andthe like. In other embodiments, the conductive material is acarbonaceous material such as carbon blacks, graphite, coke, C₆₀, andthe like. In still other embodiments, the conductive material is acharge transfer complex such astetramethylparaphenylenediamine-chloranile, alkali metaltetracyanoquinodimethane complexes, tetrathiofulvalene halide complexes,and the like. In other embodiments, the conductive material is aninorganic conductor such as a metal or a metal alloy. Examples includeAg, Au, Cu, Pt, AuCu alloy, and the like. In other embodiments, theconductive material is a highly doped semiconductor. Examples includeSi, GaAs, InP, MoS₂, TiO₂, and the like. In still other embodiments, theconductive material is a conductive metal oxide. Examples include In₂O₃,SnO₂, Na_(x)Pt₃O₄, and the like. In other embodiments, the conductivematerial is a superconductor. Examples include YBa₂Cu₃O₇, T1₂Ba₂Ca₂Cu₃O₁₀, and the like. In still other embodiments, the conductivematerial is a mixed inorganic/organic conductor. Examples includetetracyanoplatinate complexes, iridium halocarbonyl complexes, stackedmacrocyclic complexes, and the like.

Certain embodiments include a second chemically sensitive resistor thathas a resistance. The second resistor includes a combination of a firstnonconductive organic material that has a resistance, a secondnonconductive organic material that has a resistance, and a conductivematerial. The resistance of the second chemically sensitive resistor isnonlinear, using the definition provided herein.

In certain embodiments having at least two resistors, the firstnonconductive organic material in the first resistor is the same as thefirst nonconductive organic material in the second resistor, and incertain of these embodiments, the mole fraction of the firstnonconductive organic material in the first chemically sensitiveresistor is different from the mole fraction of the first nonconductiveorganic material in the second chemically sensitive resistor. In certainof the embodiments just described, the ratio of the resistance of thefirst resistor to the resistance of the second resistor is a function ofa property different from the ratio of the mole fraction of the firstnonconductive organic material in the first resistor to the molefraction of the first nonconductive organic material in the secondresistor, which is yet another example of the nonlinearity of theseembodiments. In other embodiments, the second nonconductive organicmaterial in the first resistor is the same as the second nonconductiveorganic material in the second resistor.

In embodiments with one or more conductive materials, where the sensorsswell in response to contact with a chemical analyte, the particles ofconductive material in the sensors move farther apart, therebyincreasing the resistance to electrical current passing through thesensor. As such, in embodiments where a conductive material is added tothe sensors, the sensors will provide (i) an electrical path, (ii) afirst electrical resistance in the electrical path in the absence of theanalyte, and (iii) a second electrical resistance in the presence of thechemical analyte. Where the sensor is incapable of sorbing the chemicalanalyte, the first and second electrical resistances will generally bethe same. However, where the sensor sorbs the chemical analyte, thesecond electrical resistance will generally be different than the firstelectrical resistance. Thus, in embodiments where the sensors includeconductive materials, the detectable signal that detects the presence ofa chemical analyte in the fluid is a direct current electricalresistance, but could be resistance over time or frequency.

The sensors that are chemically sensitive resistors can be used in avariety of ways. One embodiment is a method for detecting the presenceof an analyte in a fluid, which includes the steps of providing an arrayof sensors that includes two chemically sensitive resistors, each havinga resistance response to the fluid and a resistance response to theanalyte, and an electrical measuring apparatus electrically connected tothe resistors. Each chemically sensitive resistor includes a combinationof a first nonconductive organic material at a concentration, a secondnonconductive organic material, and a conductive material, with theproviso that the first nonconductive organic material in each resistoris different from the second nonconductive organic material in eachresistor and with a further proviso that the concentration of the firstnonconductive organic material in the first resistor is different fromthe concentration of the first nonconductive organic material in thesecond resistor. The resistors are then exposed to the fluid andresistance responses that occur when the resistors are permeated by thefluid are measured. Then, the measured resistance response of the firstresistor is compared to the measured resistance response of the secondresistor to determine the presence of the analyte in the fluid.

As indicated previously herein, certain embodiments of this methodinclude nonconductive organic materials that are nonconductive organicpolymers. Other embodiments include nonconductive organic materials thatare monomers. In some embodiments, the first organic monomer or polymeris different from the second organic monomer or polymer. In embodimentsincluding monomers, the monomers are polymerized to form an organicpolymer. Polymerization is induced by exposure of the monomers to anactivating agent, such as light, heat or catalytic chemical. In certainembodiments containing more than one resistor, the first organicmaterial in the first resistor is the same as the first organic materialin the second resistor and the second organic material in the firstresistor is the same as the second organic material in the secondresistor. In certain of these embodiments, the concentration of thefirst organic material in the first resistor is different from theconcentration of the first organic material in the second resistor.Thus, a concentration gradient of the first organic material is formedacross the resistors in the combinatorial resistor array. Similarly, aconcentration gradient of the second organic material is formed acrossthe resistors, as well.

Certain embodiments containing at least two resistors further includethe step of providing a known sample of the analyte in solution andexposing the first and second chemically sensitive resistors to theknown solution to create a known response pattern to the presence of theanalyte. Then, when the sensors are exposed to an unknown fluid, thefirst measured response and the second measured response are used tocreate a measured response pattern. This measured response pattern canthen be compared to the known response pattern to determine the presenceof the analyte in the fluid, the absence of a substance different fromthe analyte in the fluid or the concentration of the analyte in thefluid.

In other embodiments, an information storage device is coupled to theelectrical measuring apparatus, and the method includes the additionalstep of storing information in the storage device. This informationstorage device can be coupled to embodiments having one or more sensors.In some embodiments, this information storage device is a computer. Incertain embodiments the stored information is the resistance response tothe analyte for each resistor. In other embodiments, the storedinformation is the resistance response of the resistor as a function oftime.

In embodiments that have at least two sensors, the stored informationcan be the known response pattern to the analyte. The method thenincludes the additional step of comparing the measured response patternto the known response pattern to determine the presence of the analytein the fluid, the absence of a substance different from the analyte inthe fluid or the concentration of the analyte in the fluid.

In some embodiments, the electrical measuring apparatus includes anintegrated circuit. In certain embodiments, the integrated circuitincludes neural network-based hardware. In other embodiments, theintegrated circuit includes a digital-analog converter.

The methods of fabrication of the sensors described herein allow quick,easy and inexpensive preparation of large numbers of chemicallysensitive sensors in a combinatorial fashion. In one embodiment, arraysof compositionally distinct sensors are incorporated into a device thatis designed to detect the presence of an analyte in a fluid by providinga detectable response. Such devices include, without limitation, surfaceacoustic wave sensors, quartz crystal microbalance sensors,polymer-coated fiber optic sensors, devices designed as analogs of themammalian olfactory system, and the like. In such systems, the array ofsensors employed often comprises at least ten, usually at least 100, andoften at least 1000 different sensors, though with mass depositionfabrication techniques described herein or otherwise known in the art,arrays of on the order of at least 10⁶ sensors are readily produced. Incertain embodiments, arrays of sensor are placed in communication withan apparatus designed to detect and/or measure the signal produced bythe sensor array both in the presence and in the absence of the chemicalanalyte of interest.

As discussed previously, the sensors described herein can be combinedwith a wide variety of supporting technology to measure sensor responseother than resistance. These embodiments include techniques that detectvariations in electromagnetic energy, optical properties, capacitance,inductance or impedance and other physical, chemical and electricalproperties that may vary in accordance with the response of the sensors.Thus, the applications to which the sensors may be put is very broad.

One embodiment is a sensor that includes two chemically sensitiveelements. The first chemically sensitive element, which includes acombination of first and second organic materials, is adapted to providea detectable response. The organic materials can be any of the suitablematerials previously described herein. The detectable response of thisfirst element is nonlinear by the definition provided herein. The secondchemically sensitive element, which also includes a combination of firstand second organic materials, is also adapted to provide a detectableresponse. The detectable response of the second element is alsononlinear by the definition provided herein. A detector is operativelyassociated with the first and second chemically sensitive elements.During use, each of the first and said second chemically sensitiveelements gives a detectable response when in contact with the analyte,which is different from the detectable response when the first andsecond elements are free of the analyte. In some embodiments, thedetectable response is a variation in optical transmission and thedetector is a spectrophotometer. In other embodiments, the detectableresponse is a variation in electromagnetic energy, and the detectormeasures electromagnetic energy.

Other embodiments include methods by which the above-described sensorscan be used. One embodiment is a method for detecting the presence of ananalyte in a fluid, which first includes the step of providing a firstchemically sensitive element as described in the immediately precedingparagraph, where the element has a detectable response to the fluid anda detectable response to the analyte. A second chemically sensitiveelement is also provided which has a detectable response to the fluidand a detectable response to the analyte. A detector is operativelyassociated with the first and second chemically sensitive elements.Next, the first and second chemically sensitive elements are exposed tothe fluid. Then the detectable response of the first element ismeasured. As previously described, in one embodiment, this detectableresponse is optical transmission. In another embodiment, the detectableresponse is electromagnetic energy. This detectable response of thefirst element is nonlinear according to the definition provided herein.Next, the detectable response of the second element is measured. Thisdetectable of the second element is also nonlinear, in that it isdifferent from a sum of the detectable response to permeation by thefluid of the first organic material and the detectable response topermeation by the fluid of the second organic material, is differentfrom an average of the detectable response to permeation by the fluid ofthe first organic material and the detectable response to permeation bythe fluid of the second organic material. Next, the measured response ofthe first element is compared to the detectable response by the analytefor the first element and the measured response of the second element iscompared to the detectable response to the analyte for the secondelement to determine the presence of the analyte in the fluid.

A wide variety of chemical analytes and fluids may be analyzed by thedisclosed sensors and arrays so long as the subject analyte is capablegenerating a differential response across a plurality of sensors of thearray. Analyte applications include broad ranges of chemical classessuch as organics such as alkanes, alkenes, alkynes, dienes, alicyclichydrocarbons, arenes, alcohols, ethers, ketones, aldehydes, carbonyls,carbanions, polynuclear aromatics and derivatives of such organics,e.g., halide derivatives, etc., biomolecules such as sugars, isoprenesand isoprenoids, fatty acids and derivatives, etc. Accordingly,commercial applications of the sensors and arrays include environmentaltoxicology and remediation, biomedicine, materials quality control, foodand agricultural products monitoring, and the like.

Further details of these devices and methods are illustrated in thefollowing non-limiting examples.

EXAMPLE 1

Two organic polymers, poly(vinyl acetate)(PVA) and poly(methylmethacrylate) (PMMA), were selected to form compositionally variedsensors to determine if those sensors would be capable of providing adetectable signal which is not linearly related to the mole fraction ofeither of the organic polymers present in the sensor. Five differentPVA/PMMA blends were investigated as carbon black-containing chemicallysensitive resistors. The combinatorial sensor fabrication was achievedby combining the two initial base polymer feedstocks to producesolutions of PVA/PMMA mixtures having PVA mole fractions of 0.000,0.292, 0.551, 0.773 and 1.000, respectively. Each stock solutioncontained 25 mL of tetrahydrofuran (THF) and 250 mg total dissolvedorganic polymer, with nominally identical procedures used to fabricateall sensors. To introduce the electrically conducting carbon blackcomponent into the composite, a 10 mL aliquot of each stock solution wasthen combined with 43 mg of carbon black. Each carbon black-polymersuspension was sonicated for 10 minutes and was then spin-coated, at1000 rpm, onto a glass slide.

The sensors were allowed to dry for a minimum of 12 hours before use.Prior to sensor deposition, the glass slide was coated with two goldcontacts to allow monitoring of the resistance response of the sensorsupon exposure to various test vapors.

FIG. 1 displays a typical sensor response. Upon exposure to a test vaporcontaining 13.9 ppth (parts per thousand) of methanol in air for 540seconds starting at the time point designated 180 seconds in the graph,the resistance of the composite film increases and the response thendecreases after the vapor exposure is terminated. This behavior has beendiscussed in detail for a series of pure polymeric compositions thathave been used as either carbon black or polypyrrole composites toprovide arrays of electrically conductive vapor sensors. Lonergan etal., Chem. Mater. 8:2298 (1996) and Freund and Lewis, Proc. Natl. Acad.Sci. USA 92:2652 (1995). Specifically, the increase in electricalresistance observed in response to contact with the chemical analyte isa result of the polymeric material of the sensor sorbing the analyte,thereby swelling and increasing the distance between at least some ofthe carbon black particles present in the sensor and, in turn,increasing the relative electrical resistance.

To assess the performance of the miscible blend sensors, all of thesensors were exposed five times each to five different analytes, withthe vapor concentrations arbitrarily chosen to be 13.9 parts perthousand (ppth) of methanol, 5.2 ppth of ethanol, 7.2 ppth of acetone,2.9 ppth of ethyl acetate and 4.6 ppth of acetonitrile in air at 21° C.Only the maximum differential resistance response relative to thebaseline resistance ΔR_(max)/R was used in the analysis of the arrayperformance carried out in this work. The results are presented in FIG.2.

FIG. 2 depicts a plot of ΔR_(max)/R for the polymer blend chemicallysensitive resistors upon exposure to ethyl acetate. Similar behavior wasobserved when methanol, ethanol, acetonitrile or acetone were used astest vapors (data not shown). In all cases, a statistically significantnon-linearity was observed for the sensor response versus the molefraction of the base polymer feedstocks.

This indicates that useful information is available through use of suchmiscible blend materials in a sensor array for vapor classification.

The ability of a specific sensor array to resolve pairs of solventvapors can be quantified statistically through reference to ageneralized resolution factor, rf. This quantity is equivalent to thatproposed by Muller, Sens. Actuators B 4:35 (1991) and recently used byGardner and Bartlett, Eurosensors IX, pp. 169 (1995) and is amulti-dimensional analogue to the separation factors used in gaschromatography. Nonlinearity in the gas-solid partition coefficient iscrucial to increasing the diversity of a broadly responsive sensor arraythat is fabricated through combinatorial methods, because otherwise theresponse of the blended chemically sensitive resistors can be predictedprecisely from the responses of the base polymeric sensor materials. Nonew analyte classification information is therefore provided by theinclusion of the additional sensors into the sensor array without suchnonlinear behavior.

The mean response vector,{right arrow over (X)}_(a)of an n-sensor array to analyte a is taken as the n-dimensional vectorcontaining the mean response of each sensor,Q_(aj)to the ath analyte as components such that,{right arrow over (X)}_(a)=( Q_(a1) , Q_(a2) , . . . , Q_(an) )The average separation,|{right arrow over (d)}|between two analytes, a and b, in the Euclidean sensor response space isthen just the magnitude of the difference between{right arrow over (X)}_(a)and{right arrow over (X)}_(b)

The reproducibility of the sensor responses to the analytes is alsoimportant in quantifying the resolving power of the array. Thus thestandard deviations,σ_(a,{right arrow over (d)})andσ_(b, d)obtained from all the individual array responses to each of a and b inthe direction of the vector d, are used to describe the averageseparation and ultimately define the resolution factor,

${rf} = \frac{\overset{arrow}{d}}{\sqrt{\sigma_{a,\overset{arrow}{d}}^{2} + \sigma_{b,\overset{arrow}{d}}^{2}}}$

This metric allows quantification of the ability of the sensor array toresolve pairwise the vapors of concern in the test analyte set. Becausethe functional form of the response of the various polymer chemicallysensitive resistors was very similar, this procedure can be used toprovide an objective measure of array performance, as opposed toperforming a subjective assessment of the performance of task-specificneural network classifiers on functionally dissimilar responses ofvarious array elements. Zupan and Gasteiger, Neural Networks forChemists, VCH, New York, N.Y., pp. 305 (1993).

The responses produced by a set of 12 sensors, three with only PMMA, twowith 29.2% mole fraction PVA in PMMA, two with 55.1% mole fraction PVAin PMMA, three with 77.3% mole fraction PVA in PMMA, and two with onlyPVA, were investigated using this approach. Two criteria were chosen asa measure of the performance of each array: (1) the mean resolutionfactor of the sensor array for all of the analyte pairs in the test set,and (2) the value of rf produced by that library for the worst-resolvedpair of analytes in the test set. The performance of every combinationof 5 of the 12 sensors was evaluated to determine if the best-performingset, by either performance criterion, would contain the 5 sensorscomprised of only the base polymers or whether some of thecombinatorially fabricated polymer blends would be included in thebest-performing sensor library. The results of these experiments arepresented in Tables 1 to 3.

TABLE 1 Sensor set, including combinatorial sensors, with largestaverage rf^(a) (avg. rf = 20, worst rf = 2.8) ethanol acetonitrileacetone ethyl acetate methanol 15 2.8 16 25 ethanol 25 10 19acetonitrile 32 40 acetone 15 ^(a)This set of five sensors contained onewith only PMMA.

TABLE 2 Sensor set, including combinatorial sensors, with largestaverage rf^(b) (avg. rf = 19, worst rf = 3.0) ethanol acetonitrileacetone ethyl acetate methanol 13 3.0 28 21 ethanol 24 9.4 15acetonitrile 30 33 acetone 20 ^(b)This set of five sensors contained twowith only PMMA, one with 77.3 PVA in PMMA and two with only PVA.

TABLE 3 Sensor set with only single polymer sensors^(c) (avg. rf = 14,worst rf = 3.0) ethanol acetonitrile acetone ethyl acetate methanol 123.0 19 18 ethanol 14 8.1 9.1 acetonitrile 25 20 acetone 14 ^(c)This setof five sensors contained three with only PMMA and 2 with only PVA.

As clearly shown in Tables 1–3, the inclusion of thecombinatorially-fabricated sensors produced a statistically significantimprovement in average rf. Large improvements in the resolution ofindividual vapor pairs, such as acetonitrile from ethyl acetate, orethanol from ethyl acetate, were obtained by including thecombinatorially-fabricated sensors into the sensor library. However, theperformance of the array in separating the worst resolved pair ofsolvents, methanol and acetonitrile, did not improve significantly byincluding the combinatorially-formed sensors into the library,indicating that further diversity in the base components of the array isrequired in order to optimize the performance of the array for thisparticular sensing task.

Another significant conclusion arising from the data presented in Tables1–3 is that the classification of these various vapors, at fixedconcentrations, is statistically robust from the array response eventhough the individual sensors themselves were not designed to possesshigh selectivity toward a specific analyte. For example, a pairwiseresolution factor of 8 implies that, in a single presentation of thechallenge vapors to the sensor array, a given vapor can be distinguishedfrom the other member of the test pair statistically with >99.999%confidence level. This level of performance was met or exceeded by thebest-performing five element polymer blend sensor arrays for essentiallyall of the test vapor pairs used in this work (exceptmethanol-acetonitrile, which were only distinguished at approximately a96% confidence in a single presentation), even though the array elementswere not chosen in advance specifically to perform any particular set ofvapor classification tasks.

Exploitation of a nonlinear response of binary, tertiary, and quaternaryblend chemically sensitive resistors to various solvent vapors shouldoffer the opportunity to increase significantly the diversity of apolymer composite sensor library and, therefore, to increase itsclassification performance relative to a library that containschemically sensitive resistors fabricated from the pure polymeric phasesalone.

The olfactory bulb of canines has approximately 100 million receptorcells and that humans have over 1000 different olfactory receptorproteins. Axel, Sc. Am. 154 (1995). Thus, attempts to mimic functionallythe olfactory sense are more likely to be realizable with exploitationof combinatorial sensor library methodologies to incorporate extensivediversity into a polymer-based vapor sensing array. Certain embodimentsprovide novel methods for preparing highly diverse libraries ofchemically sensitive sensors.

EXAMPLE 2

Compatible blends of poly(vinyl acetate) and poly(methyl methacrylate)have been used to produce a series of electrically conducting carbonblack composites whose resistance is sensitive to the nature andconcentration of an analyte in the vapor phase. See Lewis, Grubbs,Severin, Sanner and Doleman, “Use of Compatible Polymer Blends toFabricate Arrays of Carbon Black-Polymer Composite Vapor Detectors,”Analytical Chemistry, in press (1998), incorporated herein by referencein its entirety. The dc electrical resistance response of the compositeswas found to be a nonlinear function of the mole fraction of poly(vinylacetate) in the blend. These compatible blend composite detectorsprovided additional analyte discrimination information relative to areference detector array that only contained composites formed using thepure polymer phases. The added discrimination power provided by thecompatible blend detectors, and thus the added diversity of the enhanceddetector array, was quantified through use of a statistical metric toassess the performance of detector arrays in various vaporclassification tasks.

Eight different PVA/PMMA blend compositions were investigated as carbonblack composite chemiresistor vapor detectors. The compatible blenddetector fabrication was achieved by combining the two initial basepolymer feedstocks to produce solutions of PVA/PMMA having PVA molefractions (by monomer) of 0.00, 0.11, 0.28, 0.44, 0.64, 0.78, 0.91, and1.00, respectively. Each stock solution contained 20 mL oftetrahydrofuran, 200 mg of total dissolved polymer, and 86 mg ofsuspended carbon black. Standard glass microscope slides, cut to a sizeof approximately 2 cm×2.5 cm, were modified for use as the substrate foreach polymer blend detector. Two parallel bands of 20 nm thick chromium(≈2 cm×1 cm), spaced apart 0.5 cm, were evaporated onto each slide. Thechromium bands were then coated with 30 nm of evaporated gold, thusforming robust electrical contacts. Each carbon black-polymer suspensionwas sonicated for 10 minutes and was then spin-coated, at 1000 rpm, ontoa modified glass slide such that the gap between the slide electricalcontacts was spanned by the polymer composite film. The detectors wereallowed to dry in ambient air for 12 hours before use.

To obtain response data, the detectors were placed into a 1.2 L samplingchamber and electrical leads were attached to the two chromium-goldbands of each detector. The dc resistance of each detector was recordedas a function of time using a Keithley model 7001 channel switcherconnected to a Keithley model 2002 multimeter that was interfaced to apersonal computer. An automated flow system consisting of LabVIEWsoftware, a personal computer, and electrically controlled solenoidvalves and mass flow controllers was used to produce and deliverycontrolled concentrations of solvent vapors to the detectors in thesampling chamber. The desired vapor concentrations were obtained bypassing a stream of carrier gas through a bubbler that had been filledwith the solvent of choice and then diluting this flow into a stream ofair maintained at a controlled flow rate. The time protocol for eachexposure was 120 s of air, followed by 600 s of test vapor in air,ending with another 600 s of air.

FIG. 10 displays the resistance response of a typical detector. Uponexposure to a test vapor, the resistance of the composite filmincreased, and the response then decreased after the vapor exposure wasterminated. This behavior has been discussed in detail for a series ofpure polymeric compositions that have been used as either carbon blackor polypyrrole composites to provide different analytes, with the vaporconcentrations chosen to be 11.3 parts per thousand (ppth) of methanol,5.2 ppth of ethanol, 20.7 ppth of acetone, 8.3 ppth of ethyl acetate,and 8.2 ppth of acetonitrile in air at 21° C. these concentrations allcorrespond to 7.1% of the solvent-saturated concentration of eachanalyte in 21° C. air, under a total atmospheric pressure of 753 Torr.The maximum differential resistance response relative to the baselineresistance (ΔR_(max)/R_(b)) was used in the analysis of the arrayperformance carried out in this work.

FIGS. 5–10 depict plots of ΔR_(max)/R_(b) for the polymer blandchemiresistors upon exposure to acetate, ethanol, acetonitrile, acetone,and methanol. For each analyte, a statistically significant nonlinearitywas observed for the detector response versus the mole fraction of thebase polymer feedstocks. Since the nonlinearity is not the same for allsolvents, this indicates that useful information is available throughuse of such compatible blend materials in a detector array for vaporclassification.

The ability of a specific detector array to resolve pairs of solventvapors can be quantified statistically through reference to ageneralized resolution factor, rf. This quantity is equivalent to thatproposed by Miller et al., [need citation] and recently used by Gardnerand Bartlett [need citation] and is multidimensional analogue of theseparation factors used in gas chromatography. Resistance responses,ΔR_(max)/R_(b), of carbon black-polymer composite detectors, containing≧20 wt. % carbon black, have been shown to vary linearly over at leastan order of magnitude in the concentration of the analyte in the vaporphase. Hence, detector arrays which can resolve analytes at oneconcentration can also be used to resolve analytes at otherconcentrations. The detector responses were autoscaled to account forthe different dynamic ranges of different detectors. The autoscaledresponse of the jth detector to the ith exposure, A_(ij) was thus

$\begin{matrix}{A_{ij} = \frac{( {\Delta\;{R_{{ij},\max}/R_{b}}} ) - \alpha_{j}}{\beta_{j}}} & (1)\end{matrix}$

where αj and βj are the mean and standard deviations, respectively, inthe responses of the jth detector to all analytes. The mean responsevector, {right arrow over (x_(a))}, of an n-detector array to analyte ais taken as the n-dimensional vector containing the mean autoscaledresponse of each detector {right arrow over (A_(aj))}, to the athanalyte such that{right arrow over (x_(a))}=({right arrow over (A_(a1))},{right arrowover (A_(a2))}, . . . ,{right arrow over (A_(an))})  (2)

The average separation, |{right arrow over (d)}|, between two analytes,a and b, in the Euclidean detector response space is then simply themagnitude of the difference between {right arrow over (x_(a))} and{right arrow over (x_(b))}. The reproducibility of the array responsesto the analytes is also important in quantifying the resolving power ofthe array. A measure of array response reproducibility to analyte, a,π_(a, {right arrow over (a)}), is obtained by projecting the arrayresponse vectors for each exposure to analyte a onto the vector {rightarrow over (d)}, and calculating the standard deviation in these scalarprojections about the projection of the mean response vector, {rightarrow over (x_(a))} onto {right arrow over (d)}. The same procedure isrepeated for analyte b of the a, b analyte pair, allowing a pairwiseresolution factor to be defined as

$\begin{matrix}{{rf} = \frac{\overset{arrow}{d}}{\sqrt{\sigma_{a,\overset{arrow}{d}}^{2} + \sigma_{b,\overset{arrow}{d}}^{2}}}} & (3)\end{matrix}$

This metric allows quantification of the ability to resolve pairwise thevapors of concern in the test analyte set based on the response pattersthat they produce on the detector array. Because the functional form ofthe response of the various polymer composite chemiresistors was verysimilar, this procedure can be used to provide an objective measure ofarray performance, as opposed to performing a subjective assessment ofthe performance of task-specific neural network classifiers onfunctionally dissimilar responses of various array elements. It isimportant to realize, however, that the results are nevertheless coupledto the metric used to evaluate the response and that differentalgorithms, such as, for example, Fisher linear discriminants, which arelinear data analysis methods that are not confined to pass through themean response values of the analytes of concern, may well yielddifferent conclusions from the same response data.

The response produced by a set of 99 detectors, 14 detectors with purePMMA, 10 with 11% PVA, 10 with 28% PVA, 15 with 44% PVA, 10 with 64%PVA, 15 with 78% PVA, 10 with 91% PVA, and 15 with pure PVA, wereinvestigated using this approach. The performances of 8-detectorcombinations from different sets of detectors were evaluated todetermine if arrays containing some of the compatible blend polymerdetectors would perform better than arrays containing only detectorsmade from the base polymers, for certain test tasks. The performance ofeach studies array was measured by its ability to resolve the solventspairwise, as given by the calculated rf values obtained using the simplelinear data analysis method described above.

Results are presented for four sets of detectors. Set A contained all 14detectors with 0% PVA and all 15 detectors with 100% PVA (i.e., all thebase polymer detectors). Set B contained all 99 of the prepareddetectors ranging from 0% through to 100% PVA content. Set C containedonly the 10 detectors with 91% PVA. Set D contained all 14 of the 0% PVAdetectors, all 10 of the 91% PVA detectors, and all 15 of the 100% PVAdetectors. Since there are extremely large numbers of possible8-detector combinations from within sets A, B, and D (≈10 unique8-detector combinations out of 99 set B detectors), 500-member subsetsof the total number of 8-detector array combinations were selectedrandomly and their corresponding rf values were calculated. For set C,rf values for all 45 possible 8-detector combinations out of 10detectors were calculated. The results of the calculated resolutionfactors for arrays of 8-detectors within each set were averaged and arepresented in Table 4, below.

TABLE 4 acetate acetate Sensors Overall vs vs vs vs. vs vs vs vs vs vsused avg. rf ethanol ethyl acetate acetonitrile acetone ethyl acetateacetonitrile acetone acetonitrile acetone acetone Set A 52 25 61 90 4458 93 42 58 20 27 Set B 60 19 67 104 81 67 110 81 31 17 26 Set C 81 4.6122 102 181 103 93 148 17 31 8.7 Set D 60 23 84 93 60 82 96 58 55 22 26The overall average rf represents the average resolution factor acrossall analyte pairs for random combinations of detectors from a givendetector set. The results for set A, set B, and set D were obtained byaveraging over 500 randomly selected 8-detector arrays composed of onlythe detectors within each respective set. The results for set C wereobtained by averaging over all 45 possible 8-detector combinationsof thedetectors within the set. Set A contained all 14 of the 0% PVA detectorsand all 15 of the 100% PVA detectors (i.e., all the base polymerdetectors). Set B contained all 99 of the prepared detectors rangingfrom 0% to 100% PVA content. Set C contained only the 10 detectors with91% PVA. Set D contained all 14 of the 0% PVA detectors, all 10 of the91% PVA detectors, and all 15 of the 100% PVA detectors.

Clearly, the inclusion of compatible blend detectors produced astatistically significant improvement in maximizing the overall averagerf, which is the average ability of all calculated 8-detector arraycombinations within a set of detectors to resolve all analyte pairsusing the metric defined above. For example, sets B, C, and D, whichcontained compatible blend detectors, had overall average rf's of 60,81, and 60, respectively, whereas the base polymer detector arrays (setA) had an overall average rf of 52. The array performance in separatingthe pair of solvents, ethyl acetate vs. acetone, that was worst resolvedby set A (base polymer detectors) could also be improved by using8-detector arrays containing only 91% PVA detectors (set C) or byincluding these detectors in arrays that contained the base polymerdetectors (set D). Set D arrays, containing blended polymers, exhibit alarger overall average rf, a larger rf for the worst resolved analytepair, and resolved 7 of the 10 analyte pairs better than did the basepolymer arrays of set A.

Another significant conclusion arising from the data is that theclassification of these various vapors, at fixed concentrations, isstatistically robust from the array response even though the individualdetectors themselves were not designed to possess high selectivitytoward a specific analyte. For example, a pairwise resolution factor of4.5 implies that, in a single presentation of the challenge vapors tothe detector array, a given vapor can be . . . was met or exceeded byall of the eight-element detector arrays of Table 4 for all of the testvapor pairs used in this work, even though the array elements were notchosen in advance specifically to perform any particular set of vaporclassification tasks.

Utilization of a nonlinear response of binary, tertiary, and quaternaryblend composite chemiresistors to various solvent vapors should offerthe opportunity to increase significantly the diversity of a polymercomposite detector array and therefore to increase its classificationperformance relative to an array that contains chemiresistors fabricatedfrom the pure polymeric phases alone. The binary polymer blendadvantages reported herein are in agreement with those recentlypublished using a different detector modality, polymer-dye opticaldetectors. The exact performance gain of any specific array will likelybe task dependent and must be evaluated for each application of concern.We note, however, that the olfactory bulb of canines has approximately100 million receptor cells and that humans have over 1000 different . .. into a polymer-based vapor-sensing array. Extension of the approachdescribed herein to other blends and a comparison of the detectordiversity that can be achieved through the use of block and randomcopolymers as a complement to the use of compatible blends in detectorarrays will be reported separately.

While particular devices and methods have been described for producingcompositionally different polymer-based sensors, once this descriptionis known, it will be apparent to those of ordinary skill in the art thatother embodiments and alternate steps are also possible withoutdeparting from the spirit and scope of the invention. Moreover, it willbe apparent that certain features of each embodiment as well as featuresdisclosed in each reference incorporated herein, can be used incombination with devices illustrated in other embodiments. Accordingly,the above description should be construed as illustrative, and not in alimiting sense, the scope of the invention being defined by thefollowing claims.

1. A method of manufacturing a combinatorial sensor array for detectingan analyte in a fluid, comprising the steps of: providing a firstsolution of a first organic material at a concentration x in a firstsolvent, a second solution of a second organic material at aconcentration y in a second solvent, and a substrate having a firstpreselected region and a second preselected region; contacting saidfirst region with said first solution at said concentration x;contacting the second region with the first solution at saidconcentration x+a; contacting the first region with said second solutionat said concentration y; and contacting the second region with thesecond solution at said concentration y+b, wherein, the first regionforms a first sensor having a blend of the first organic material atmole fraction m and the second organic material at mole fraction 1−m andthe second region forms a second sensor having a blend of the firstorganic material at mole fraction n and the second organic material ofmole fraction 1−n, said two sensors forming a combinatorial sensorarray, wherein the sensor array is configured to be optically connectedwith a detector, wherein the first region and the second region on thesubstrate are physically separated, and wherein the first region isrecessed below the surface of the substrate in a first well and thesecond region is recessed below the surface of the substrate in a secondwell, the first well physically separated from the second well.
 2. Themethod of claim 1, wherein m=n.
 3. The method of claim 1, wherein x=y.4. The method of claim 1, wherein a=b.
 5. The method of claim 1, whereina and b are positive numbers.
 6. The method of claim 1, wherein a and bare negative numbers.
 7. The method of claim 1, wherein the firstorganic material is a first polymer.
 8. The method of claim 1, whereinthe second organic material is a second polymer.
 9. The method of claim1, wherein the first organic material is a first polymer and the secondorganic material is a second polymer.
 10. The method of claim 9, whereinthe first polymer is different from the second polymer.
 11. The methodof claim 1, wherein the first organic material is a first monomer, andfurther comprising the step of: polymerizing said first monomer byapplying an activating agent to the first region and to the secondregion.
 12. The method of claim 11, wherein said activating agent isselected from the group consisting of light, heat and chemical.
 13. Themethod of claim 1, wherein the second organic material is a secondmonomer, and further comprising the step of: polymerizing said secondmonomer by applying an activating agent to the first region and to thesecond region.
 14. The method of claim 13, wherein said activating agentis selected from the group consisting of light, heat and chemical. 15.The method of claim 1, wherein the first solution is miscible in thesecond solution.
 16. The method of claim 15, wherein said first solventis the same as said second solvent.
 17. The method of claim 1, whereinthe step of contacting comprises spraying.
 18. The method of claim 1,wherein the step of contacting comprises a step selected from the groupconsisting of coating, pipetting, micropipetting, depositing, spinning,evaporating, dipping and flowing.
 19. The method of claim 1, wherein,after the step of contacting said first region with said first solutionat said concentration x, the method further comprises the step ofvarying the concentration of the first organic material in the firstsolution to concentration x+a.
 20. The method of claim 19, wherein theconcentration of the first organic material in the first solution issmoothly varied to concentration x+a.
 21. The method of claim 19,wherein, after the step of varying the concentration of the firstorganic material in the first solution to concentration x+a, the methodfurther comprises the step of moving the first solution to said secondregion.
 22. The method of claim 1, wherein, after the step of contactingsaid first region with said second solution at said concentration y, themethod further comprises the step of varying the concentration of thesecond organic material in the second solution to concentration y+b. 23.The method of claim 22, wherein the concentration of the second organicmaterial in the second solution is smoothly varied to concentration y+b.24. The method of claim 1, wherein, after the step of varying theconcentration of the second organic material in the second solution toy+b, the method further comprises the step of moving the second solutionto said second region.
 25. A method of manufacturing a combinatorialsensor array for detecting an analyte in a fluid, comprising the stepsof: providing a first solution of a first organic material at aconcentration x in a first solvent, a second solution of a secondorganic material at a concentration y in a second solvent, and asubstrate having a first preselected region and a second preselectedregion; contacting said first region with said first solution at saidconcentration x; contacting the second region with the first solution atsaid concentration x+a; contacting the first region with said secondsolution at said concentration y; and contacting the second region withthe second solution at said concentration y+b, wherein, the first regionforms a first sensor having a blend of the first organic material atmole fraction m and the second organic material at mole fraction 1−m andthe second region forms a second sensor having a blend of the firstorganic material at mole fraction n and the second organic material ofmole fraction 1−n, said two sensors forming a combinatorial sensorarray, wherein the sensor array is configured to be optically connectedwith a detector, wherein the first region and the second region on thesubstrate are physically separated, and wherein the first region issurrounded by ridges on the surface of the substrate and the secondregion is surrounded by ridges on the surface of the substrate, thefirst region physically separated from the second region.
 26. The methodof claim 25, wherein said ridges are formed from photodefinablematerial.
 27. The method of claim 25, wherein said ridges are formedfrom sputtered material.
 28. The method of claim 1, wherein thesubstrate further comprises a third preselected region and a fourthpreselected region, the four preselected regions arranged in an array,the array having a top edge, a bottom edge, a left edge and a rightedge, the top edge adjacent to regions 1 and 2, the bottom edge adjacentto regions 3 and 4, the left edge adjacent to regions 1 and 3, and theright edge adjacent to regions 2 and 4, and further comprising the stepsof: contacting said first region and said second region near said topedge of said array with said first solution at concentration x;contacting said third and fourth regions with the first solution atconcentration x+a contacting the first and third regions near said leftedge of the array with said second solution at concentration y; andcontacting the second and fourth regions with the second solution atconcentration y+b, wherein, each region forms a sensor having a blend ofthe first organic material and the second organic material, said sensorsforming a combinatorial sensor array.
 29. The method of claim 28,wherein the mole fraction of the first organic material in the firstsensor is e, in the second sensor is f, in the third sensor is g and inthe fourth sensor is h.
 30. The method of claim 29, wherein e, f, g andIt are all different numbers.
 31. The method of claim 28, wherein, afterthe step of contacting said first region and said second region near thetop edge of said array with said first solution at concentration x, themethod further comprises the step of varying the concentration of thefirst organic material in the first solution to concentration x+a. 32.The method of claim 31, wherein the concentration of the first organicmaterial in the first solution is smoothly varied to concentration x+a.33. The method of claim 31, wherein, after the step of varying theconcentration of the first organic material in the first solution toconcentration x+a, the method further comprises the step of moving thefirst solution from near the top of the array in the direction of saidbottom of the array.
 34. The method of claim 28, wherein, after the stepof contacting said first and third regions near the left edge of saidarray with said second solution at concentration y, the method furthercomprises the step of varying the concentration of the second organicmaterial in the second solution to concentration y+b.
 35. The method ofclaim 34, wherein the concentration of the second organic material inthe second solution is smoothly varied to concentration y+b.
 36. Themethod of claim 34, wherein, after the step of varying the concentrationof the second organic material in the second solution to concentrationy+b, the method further comprises the step of moving the second solutionfrom near the left edge of the array in the direction of said right edgeof the array.